RT Journal Article
SR Electronic
T1 Inhibition of ischemia-induced subcellular redistribution of lysosomal enzymes in the perfused rat heart by the calcium entry blocker, diltiazem.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 1109
OP 1113
VO 242
IS 3
A1 K Ichihara
A1 T Haneda
A1 S Onodera
A1 Y Abiko
YR 1987
UL http://jpet.aspetjournals.org/content/242/3/1109.abstract
AB Effect of diltiazem on subcellular distribution of lysosomal enzymes, high-energy phosphate metabolism and mechanical function in the ischemic heart was studied. Ischemia was induced by lowering the afterload pressure of the perfused working rat heart. The activities of cathepsin D, beta,N-acetylglucosaminidase and acid phosphatase were determined in the nonsedimentable and sedimentable fractions after centrifugation of the tissue extract to assess the subcellular distribution of lysosomal enzymes. After ischemia, decreases in the mechanical function and the tissue level of high-energy phosphates were observed. In addition, ischemia caused subcellular redistribution of lysosomal enzymes from the lysosomes to the cytoplasm. Reperfusion of the ischemic heart did not restore the mechanical function and the level of high-energy phosphates completely. Diltiazem (2.21 X 10(-6), 1.11 X 10(-5) and 2.21 X 10(-5) M) was provided for the heart 5 min before the onset of ischemia. Diltiazem preserved high-energy phosphates in the ischemic heart, and inhibited the subcellular redistribution of lysosomal enzymes being caused by ischemia, depending on its concentration. Reperfusion after ischemia with diltiazem recovered the mechanical function that had been decreased by ischemia. These results may indicate that diltiazem can protect the myocardium against ischemic damage.